The COVID-19 pandemic has claimed the lives of more than 4.45 million people worldwide (accessed August 26, 2021) (1), and led to substantial concerns for inflammatory bowel disease (IBD) patients due to the presence of dysbiosis and immunocompromised status, despite studies demonstrating similar risk and mortality between patients with IBD and the general population (2). The pandemic significantly affected the daily lives of patients with IBD compared with non-IBD patients (3). The fear of SARS-CoV-2 infection in patients with IBD is more pronounced, especially in those taking immunosuppressants (3, 4). IBD treatments involve many immunosuppressive medications controlling an overactive immune response to induce and maintain clinical remission (5). The long-term systemic corticosteroid (especially prednisone > 20 mg/day), sulfasalazine/mesalamine and thiopurine usage is associated with an increased risk of severe COVID-19, whereas tumor necrosis factor (TNF) antagonist therapy is not (6, 7). The management of IBD during the COVID-19 pandemic has been a challenge for clinicians and patients. Based on the suggestions of experts, IBD therapies other than prednisone should be continued to sustain remission in patients not infected with SARS-CoV-2 (5, 8). However, prednisone, thiopurines, methotrexate, and tofacitinib should be stopped if patients with IBD test positive for SARS-CoV-2 or develop COVID-19 (5, 8, 9). The use of biologics should be comprehensive, based on the severity of COVID-19 and IBD (5, 8).

Efforts have been made to prevent patients with IBD from COVID-19, including the management and treatment guidelines for patients with IBD (8, 9) and the development of related studies (10, 11). The development of safe and effective vaccines is the best way to mitigate against the risk of COVID-19 and prevent the situation from worsening. Despite the promising effectiveness and safety of the candidate vaccines, immunocompromised patients or patients on immunosuppressant medications were excluded from these studies (12–14), thus creating concerns regarding the safety and generalizability of outcomes for IBD individuals (15). Furthermore, patients with IBD on immune-modifying therapies have a higher risk of suboptimal vaccine response and unknown safety (16–18).

China began its COVID-19 vaccination campaign on December 19, 2020, for people at a higher risk of infection, such as the personnel responsible for the inspection and quarantine of the imported or exported cold-chain goods (products or materials that are required to be stored at a specific low temperature), the medical and health workers, and the transportation personnel. Since January 09, 2021, the campaign was extended to the general public unless they were in an active or uncontrolled stage of chronic disease, having acute disease, pregnant, allergic to vaccine components, and having other contraindications evaluated by experts (http://www.gov.cn). At the time of the survey, one type of inactivated viral vaccine was available for Chinese and four other vaccines (two inactivated vaccines, one recombinant protein vaccine, and one adenovirus vector vaccine) were in Phase III clinical trial. Internationally, IBD populations are suggested to use SARS-CoV-2 vaccines as soon as possible regardless of immune-modifying therapies (19, 20). However, in China, at present, there are no official recommendations about whether or not patients with IBD could take the vaccination. It is mainly based on their wish after seeking medical advice from their physicians or other authoritative resources. Therefore, we designed this questionnaire to investigate the attitudes and views of individuals with IBD on COVID-19 vaccines with the aim of achieving a better understanding of vaccine acceptance and/or hesitancy in this particular population.

From December 31, 2020, to January 3, 2021, a total of 543 electronic questionnaires were returned. We confirmed that all of them were complete, standardized, and qualified for analysis (543/543), with an effective rate of 100%. Our questionnaire covered 106 cities in 26 provinces of China. Areas with COVID-19 cases or new confirmed COVID-19 cases within 14 days were considered as a medium- to high-risk areas of COVID-19 based on the criteria set by the government (http://www.gov.cn). In our study, 63.2% of participants were from the area with medium-to-high COVID-19 risk in the past and/or at present. Less than one in six (15.3 %) patients or their family members had medical or biomedical backgrounds. Table 1 demonstrates the demographics of participants and their exposure to COVID-19.

The COVID-19 pandemic has brought great trouble and concerns for patients with IBD. In our present survey, 63.2% of patients came from the COVID-19 risk area and 1.1% of those patients had a positive history of SARS-CoV-2 infection (Table 1). Safe and effective vaccines are expected by health authorities and the medical community as the most powerful weapon against the COVID-19 pandemic (21), and nearly 80.0% of respondents in our study also recognized that SARS-CoV-2 vaccination was critical to the self-health and health of others.

Willingness to be vaccinated matters greatly, for the reason that a sufficient vaccination rate in a population is indispensable before herd immunity is achieved. The published expert consensus and opinions recommend vaccinating all IBD populations as soon as they are able to receive SARS-CoV-2 vaccines (15, 19, 20). In the present study, COVID-19 vaccination hesitancy existed in 50.7% of patients with IBD and merely 16.0% of participants opted for vaccination (Figure 1). The attitude of the participants towards the COVID-19 vaccine was significantly more negative than that of the general population in China and the patients with IBD from other countries (22–24). It was reported that 67.1% of the general population in China were willing to accept the COVID-19 vaccination during the same period (22). Furthermore, the rate of vaccination intent among IBD participants in our present study was lower than that among the IBD population in Boston (80.9%) (23) and Italy (80.3%) (24). Similarly, a lower rate of intent for hepatitis B (18.8%) and varicella vaccines (6.6%) was observed among patients with IBD in China (25). The potential reasons could be the insufficient knowledge about vaccination and many concerns about vaccine safety in this specific population, as reflected in our study and other reports (16–18, 23).

Gender was found to be one of the determinants of attitude towards COVID-19 vaccination in this study (Figure 2A), in agreement with several other surveys (26, 27). The reasons for vaccination hesitancy in the female group needs to be further explored in the future, for concerns regarding reproductive impact, personality trait, and others. Patients with IBD with medical or biomedical background had a higher rate of immediately getting vaccinated (Figure 2B), and 21.7% of the respondents considered the recommendations of their attending physicians as one of the three main reasons for getting vaccinated (Figure 3B). An anonymous cross-sectional survey conducted among Chinese adults reported that the recommendation of the doctor was a contributing factor in the decision-making for vaccination (27). As recommended by clinical practice guidelines for vaccination of the immunosuppressed host (28), IBD specialists should share the responsibility of communicating with their patients about the recommendations and appropriate vaccinations amidst the COVID-19 pandemic.

Most vaccines are broadly recommended for patients with IBD, including the COVID-19 vaccines (19). However, the vaccine hesitancy and unwillingness are particularly pronounced among patients with IBD mainly due to the unpredictable outcome amidst disease activity and immunocompromised status, together with the blunted immunogenicity of some vaccines found in the immune-modifying therapies (16–18, 23, 29). Similarly, we demonstrated that the acceptance of COVID-19 vaccination was lower in participants being treated with immune-modifying therapies, especially in those using immunosuppressants (Figures 2C,D). Moreover, previous clinical studies of COVID-19 vaccines have excluded patients with immune conditions (12–14), thus heightening the concerns of patients with IBD about the safety and generalizability of the outcomes (15). We found that safety and adverse events, personal hypoimmunity, as well as efficacy and validity of COVID-19 vaccines are the top three concerns of patients with IBD for COVID-19 vaccination (Figure 3B). This phenomenon was commonly shared in the IBD populations from other countries (23). Therefore, the expert panel suggested that patients with IBD receiving SARS-CoV-2 vaccination should be referred to prospective registries tracking the amplitude and duration of immune responses across different vaccine platforms (19).

Although half of the patients with IBD were undecided about SARS-CoV-2 vaccination, participants who realized the vital importance of vaccination to self-health or the health of others had a higher intention for immediate or later vaccination when compared to those who did not fully appreciate its importance (Figures 2E,F). This result highlights the role of health education (23, 25) and recommendations from authoritative sources, such as government and IBD specialists, in removing some barriers along the process of vaccination (Figure 3B).

The vaccine candidates can be grouped into protein subunit vaccines, nucleic acid vaccines, whole-inactivated viral vaccines, live attenuated viral vaccines, and others (30). In China, more than 177.7 million doses of vaccines have been administrated to the general population (accessed August 6, 2021) (1). In general, the patients with IBD can safely receive the inactivated vaccines for vaccine-preventable diseases irrespective of immune conditions (19, 29), which may be the reason that the inactivated COVID-19 vaccine was the most popular of the four types of vaccines (Figure 1B). In reality, the types of SARS-CoV-2 vaccines including the inactivated vaccine, messenger RNA vaccines, replication-incompetent vector vaccines, and recombinant vaccines are considered safe for patients with IBD (19). The BNT162b2, ChAdOx1 nCoV-19, and mRNA-1273 vaccines have received regulatory approval in the United Kingdom, which applies to patients with IBD, indicating that an immunosuppressed state is not a contraindication (20). Even so, more research should be carried out highlighting the safety and efficacy of COVID-19 vaccines in this particular population.

This study has some limitations. First, we conducted the survey via an electronic questionnaire. Thus, although the disadvantages of the paper questionnaire, such as skipped questions or the time-consuming task of uploading the collected data, were avoided, the data of patients who could not operate electronic devices were lost. Second, response bias inherent to the online survey and an abbreviated study period may have led to an inaccurate understanding of vaccination intent. Finally, our survey results did not completely represent the attitude or the concerns of IBD populations on COVID-19 vaccination from other countries, due to different situations of the pandemic globally.

In conclusion, this study discloses COVID-19 vaccination hesitancy and paucity of knowledge about the COVID-19 vaccines in the IBD population. Further studies evaluating the efficacy and safety of various COVID-19 vaccines in IBD individuals, with a specific focus on the impact of immune-modifying therapies and serologic responses, should be carried out to alleviate the concerns of such patients. Health education and recommendation from authoritative sources, such as government and IBD specialists, may facilitate COVID-19 vaccination efforts.

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

This study was approved by the Second Affiliated Hospital of Nanjing Medical University institutional ethical review board ([2020]KY106).

FZ, BC, GJ, XW, and JL designed the study. XW did the statistical analysis. XW and JL drafted the manuscript. HB edited the manuscript for professional English. QD, BC, and GJ were involved in the revision of the manuscript. All authors have read and approved the final version of this manuscript.

This study was supported by the publicly donated Intestine Initiative Foundation; the National Natural Science Foundation of China (81600417); and the 789 Outstanding Talent Program of SAHNMU (789ZYR20200802250).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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